Thread by @michaelzlin

I've been getting 2 questions a lot:
1. If I'm J&J and I boost with Moderna/Pfizer, do I need a 2nd dose of Moderna/Pfizer?
2. If I'm J&J and I boosted with Moderna/Pfizer once, when should I boost again?

Answers:
1. Congrats, you've chosen wisely to boost your J&J with Moderna or Pfizer. After 1 shot of either, you'll have more antibodies than people after 2x Moderna or 2x Pfizer
2. After you've boosted your J&J with Moderna or Pfizer, you're good for at least 6 months (vs Delta)

Now the evidence. We all remember the NIH-sponsored heterologous boost study that measured antibody levels in people who got each of the 3 vaccines in the US, boosted by a single dose of any of the 3 vaccine types (9 combinations).

pubmed.ncbi.nlm.nih.gov/34671773/

The report came out between my birthday and the FDA VRPBAC meeting to discuss J&J boosters so it was a busy week. Seems like ages ago, but it was just 2 months. Alas the paper is still in p̶e̶e̶r̶ snail review. Also the paper has some pretty impenetrable figures such as below

Colors don't add info, booster is listed above primary so it's out of order, what should be 3x3 matrices are broken up into 3 columns of 3 subcolumns😱

Much better to look at just 15day nAb levels as a 3x3 matrix, below from ACIP ppt

Except columns/rows are different orders 😠

Let's fix that. Much better now. Now columns and rows are in the same order, from weakest to strongest.

Too bad how some authors don't take the 1 minute to make their data more understandable. Still some weird font sizes. Those are from the original figure; wasn't me.

The red/blue/green numbers above are different ways of measuring neutralizing antibody (nAb) titers. The green units are the newest WHO standard, in units of IU50/mL. 100 IU50/mL protects 90% against disease (per the even more impenetrable paper below)
science.org/doi/10.1126/sc…

That's for original strain; for Delta you need ~400. (Not clear for omicron, but expected to be higher than that.) So I circled all the numbers that are ≥400 or are statistically indistinguishable from 400 (close enough).

Also translated vaccine names into American English

And then finally, what are peak nAb levels for Moderna and Pfizer after dose 2, for comparison? Actually can't find Pfizer in WHO units anywhere, but we know Moderna has higher nAbs than Pfizer, and Moderna's number is 247 IU50/mL (Table 1 in the Science paper — not easy to find)

If you compare the green numbers here to 2x Moderna's peak # of 247, you see #JnJers will have higher nAbs after boosting with 1 dose of Pfizer (30mcg) or Moderna 100mcg. The official Moderna booster dose is 50mcg, so likely will be in between the Pfizer and Moderna numbers here.

And since you get to ≥341 IU50/mL after a Pfizer or Moderna50 boost, then you have 138% the antibodies on average compared to fresh 2x Moderna. Moderna was known to keep 70% activity against Delta cases for 6mo. So you're good for at least 6mo vs Delta.

Omicron may top our ability to prevent cases with current vaccines, but if it's not more inherently virulent then it's likely the memory B cells initiated by the vaccines would produce new antibodies to help clear the virus before severe disease as below

https://mobile.twitter.com/michaelzlin/status/1432056573124247553

That's why it's too early to be thinking about going to super-high levels of antibodies with additional boosts of the current vaccines (in case you were wondering). May not have much effect compared to the levels we have already. Best for now to wait to get more data on omicron.

BTW CDC really should be paying someone to do this, not relying on internet volunteers who are willing to shirk their day job.

People are still asking questions that are answered in the chart, so I added more explicit labels to each cell in the chart.

A "Pfizer vaccine" is two doses. So if you're wondering what happens after 3 doses for example, look up Pfizer primary and Pfizer boost. 2+1=3.

Kind of related, today the CoV-Boost trial results from the UK were finally released. Seems like ages ago when this was announced, but it was only May 19 (gov.uk/government/new…). In SARSCoV2 speed, that is eons, I guess.

thelancet.com/journals/lance…

CoV-Boost studied 7 vax types as boosters for AZ+AZ or PF+PF primary vaccinations. Nicely they looked at antibodies and T cells. Here are the results for AZ+AZ primary vaccinations. Clearly the NRA vaccines do better for antibodies (BNT=Pfizer/BioNtech, m1273=Moderna).

You can see T cell responses are similar for NVX (Novavax), Ad26 (J&J), and the RNA vaccines.

Not surprising to me that the acclaimed T-cell stimulation by J&J is similar to Pfizer and worse than Moderna. In previous posts I pointed this out from the primary vaccination.

Pleasantly surprised Novavax has as good T cell responses as Ad26 and Pfizer. Data on its T cell responses had been lacking.

But T cell function is very age-dependent. This should give caution to those who claim T cell responses will save everyone. Not everyone unfortunately.

And here are the same boosters tested after PF+PF primary vaccination. The antibody differences are smaller but still RNA > JJ ~ AZ (ChAd) ~ NVX. T cell stimulation goes Moderna > Pfizer (BNT) ~ JJ ~ AZ > NVX

Some fold changes are misleading because AZ+AZ (graph A) starts with 4x lower Ab levels than PF+PF, but similar T cells (see #s on the left side). We knew this before of course (similar for JJ).

Would have preferred they plotted absolute levels not relative change on the right.

Overall the data are best summarized as RNA serving as the best booster for both antibodies and T cell function. However I do think (as I've said elsewhere) that if you're Moderna+Moderna vaccinated, you might try a JJ booster to give you extra T cell diversity.

typo; RNA vaccines of course.

Also the T cell boost NVX shows here suggests those with NVX primaries should have good T cell function too. And we already know 2x NVX gives high antibodies between 2x Pfizer and 2x Moderna. That's convenient because of its stability in the fridge.

Why NVX didn't boost T cells in RNA-vaxxed as well as in Ad-vaxxed is a mystery. In cellular immunology speak, that means T cells expanded by Ad vaccination are restimulated by cytokines or cell-cell interactions activated by NVX, more so than T cells expanded by RNA vax.

Perhaps the Ad-expanded T cells tend to live in places that are stimulated well by subsequent NVX, better than RNA-expanded T cells. Since case and hospitalization protection seem to correlate with antibody levels, doesn't seem to matter where your T cells want to reside.

The two vaccines that really didn't work as boosters are Curevac (which is a RNA vaccine that failed its trials, so I should clarify my use of "RNA vaccines" above refer only to Pfizer and Moderna) and the inactivated whole-virus Valneva. Both these require refrigeration only.

Thus, vs other refrigeration-compatible vaccines (AZ, J&J, Valneva, Curevac), Novavax had better Ab responses as a primary vaccine, and similar or better Ab boosting. It also boosted T cells better than Valneva and Curevac. Thus it could be the best overall fridge-compatible vax.